ArticleThe Journal of general physiology2001
Blocker state dependence and trapping in hyperpolarization-activated cation channels: evidence for an intracellular activation gate.
Article in The Journal of general physiology, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers.
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88 citing papers in PubMed, 170 citations in OpenAlex.
- Structural determinants of ivabradine block of the open pore of HCN4.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Loose Coupling between the Voltage Sensor and the Activation Gate in Mammalian HCN Channels Suggests a Gating Mechanism.International journal of molecular sciences · 2024Article
- Single shot detection of alterations across multiple ionic currents from assimilation of cell membrane dynamics.Scientific reports · 2024Article
- Inhibition of HCN1 currents by norquetiapine, an active metabolite of the atypical anti-psychotic drug quetiapine.Frontiers in pharmacology · 2024Article
- HCN-Channel-Dependent Hyperexcitability of the Layer V Pyramidal Neurons in IL-mPFC Contributes to Fentanyl-Induced Hyperalgesia in Male Rats.Molecular neurobiology · 2023Article
- An evolutionarily conserved pacemaker role for HCN ion channels in smooth muscle.The Journal of physiology · 2023Article
- Review: HCN Channels in the Heart.Current cardiology reviews · 2022Review
- A second S4 movement opens hyperpolarization-activated HCN channels.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Discovery of Novel HCN4 Blockers with Unique Blocking Kinetics and Binding Properties.SLAS discovery : advancing life sciences R & D · 2021Article
- A family of hyperpolarization-activated channels selective for protons.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- The HCN domain is required for HCN channel cell-surface expression and couples voltage- and cAMP-dependent gating mechanisms.The Journal of biological chemistry · 2020Article
- Modular analysis of the control of flagellar Ca2+-spike trains produced by CatSper and CaV channels in sea urchin sperm.PLoS computational biology · 2020Article
- Article
- Lens Connexin Channels Have Differential Permeability to the Second Messenger cAMP.Investigative ophthalmology & visual science · 2019Article
- Identification and characterization of a series of novel HCN channel inhibitors.Acta pharmacologica Sinica · 2019Article
- cAMP binds to closed, inactivated, and open sea urchin HCN channels in a state-dependent manner.The Journal of general physiology · 2019Article
- Characterization of drug binding within the HCN1 channel pore.Scientific reports · 2019Article
- Bipolar switching by HCN voltage sensor underlies hyperpolarization activation.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Dorsal BNST αThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2018Article
- Inhibition of hyperpolarization-activated cyclic nucleotide-gated channels by β-blocker carvedilol.British journal of pharmacology · 2018Article
28 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Hyperpolarization-activated cation currents (I(h)) are key determinants of repetitive electrical activity in heart and nerve cells. The bradycardic agent ZD7288 is a selective blocker of these currents. We studied the mechanism for ZD7288 blockade of cloned I(h) channels in excised inside-out patches. ZD7288 blockade of the mammalian mHCN1 channel appeared to require opening of the channel, but strong hyperpolarization disfavored blockade. The steepness of this voltage-dependent effect (an apparent valence of approximately 4) makes it unlikely to arise solely from a direct effect of voltage on blocker binding. Instead, it probably indicates a differential affinity of the blocker for different channel conformations. Similar properties were seen for ZD7288 blockade of the sea urchin homologue of I(h) channels (SPIH), but some of the blockade was irreversible. To explore the molecular basis for the difference in reversibility, we constructed chimeric channels from mHCN1 and SPIH and localized the structural determinant for the reversibility to three residues in the S6 region likely to line the pore. Using a triple point mutant in S6, we also revealed the trapping of ZD7288 by the closing of the channel. Overall, the observations led us to hypothesize that the residues responsible for ZD7288 block of I(h) channels are located in the pore lining, and are guarded by an intracellular activation gate of the channel.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.